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Hunter's Syndrome and Oral Manifestations

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Hunter's Syndrome and Oral Manifestations Literature Review Hunter’ssyndrome and oral manifestations:a review Angela TempletonDowns, DDSTim Crisp, DMDGerald Ferretti, DDS, MS Abstract Wereview the literature considering systemic and Reviewof the literature on Hunter’s syndromeand oral oral manifestations of children diagnosed with Hunter’s manifestations in pediatric dental patients including the syndrome. We review a mode of treatment for these primary and secondary systemic manifestations are pre- patients as well. sented. Numerousoral manifestations are presented as Literature review well. Basedon the cases presentedin the reviewedstudies, 6 little informationis available on oral considerations and Charles Hunter noted a rare disease in children as treatment of these children. Early restoration of the oral early as 1915. On 8- and 10-year-old brothers, he re- cavity is importantprior to treatmentof the disease itself. ported findings such as a slowed learning process, (Pediatr Dent 17:98-100, 1995) throat trouble, tonsil and adenoid operations, dull hear- ing, inguinal hernias, short stature, curiously shaped unter’s syndrome is an X-linked recessive heads, large faces, puffy eyes, saddle nose, thick lips, mucopolysaccharide disorder caused by a open mouths, large tongues, abducted arms, thick H defect in the metabolism of glycosaminogly- wrists, and a very clumsyand stiff gait. These children also suffer from increasingly frequent and severe res- cans, which results from a deficiency of the enzyme ~, iduronate sulfatase. There is an accumulation of piratory infections 2, 6 that generally increase with age. dermatan and heparan sulfates in various tissues. This syndrome is found in fewer than 20 cases per Mild and severe forms exist that are a result of mu- million births, makingthe disease the rarest form of the tagenic alleles. Hunter’s syndromeclinically resembles mucopolysaccharide disorders as reported by other mucopolysaccharide disorders such as Hurler’s, Dorfman2Carrier females generally are asymptomatic, San Filippo’s, Morquio’s, and Schere’s syndromes, though they often show decreased levels of iduronate which are autosomal recessive. Hunter’s syndrome sulfatase in serum. Clinical manifestations of Hunter’s syndrome in females are exceedingly rare with only a is the exception being transmitted as an X-linked 1’ recessive1-6 disorder. few cases reported. 12 Clarke et al22 reported the syn- Primary systemic manifestations of Hunter’s syn- dromein a karyotypically normal girl. Neufeld et a123 drome are: reported two girls with clinical manifestations of mucopolysaccharidosis type II and enzyme deficien- 1. Macrocephaly cies as well as a normal karyotype. There may be no 2. Moderate to severe developmental delay family history of mucopolysaccharide disorders when 3. Dysmorphic facies a child is diagnosed with one. Successive births or numerouschildren mayresult in a family having more 4. Skeletal abnormalities than one child with the syndromebefore the first one 5. Joint contractures has any physical signs or has been diagnosed. Despite 6. Hepatosplenomegaly genetic counseling, manypeople continue to have chil- 7. Cardiac valvular disease dren affected by this type of disorder. There are two forms of Hunter’s syndrome. Type A 8. Hirsutism is the most severe form with a life expectancy of 14-15 9. Hyperkinesis years and a muchearlier onset. Type B is a muchmilder 10. Rough and uncoordinated behavior. form with a life expectancyof 30-50 years1, 2 and physi- cal features similar to, but not as severe as those of Secondarysystemic manifestations are frequent otitis Type A. Yatziv et al.14 suggested that the presence or mediaand hearing insufficiencies. 1-3, 6-9 absence of severe mental retardation and the longevity Oral manifestations include short and broad man- of the affected individuals be distinguishing factors in dible; localized, radiolucent lesions of the jaws; flat- order to help clinically determine the difference be- tened temporomandibular joints; macroglossic tongue; tween these two forms. Younget al.15 established that conical, peg-shaped teeth with generalized wide spac- patients with Hunter’s syndromedid clearly fall into ing; highly arched palate with flattened alveolar ridges; one of two groups according to the presence or absence andhyperplastic gingiva. 1, 2, 6, 7, 10, 11 of intellectual deterioration. They also reported the 98 AmericanAcademy of PediatricDentistry PediatricDentistry - 17:2,1995 more severely affected patients showeda higher inci- sions usually are associated with unerupted first per- dence of behavioral disorders. manent molars. Lit117 and Gardner7 reported that based DorfmanI has reported Hunter’s syndrome to be on other studies that these enlarged dental follicles characterized by the accumulation of dermatan and represented pools of chondroitin sulfate B (dermatan heparan sulfate in various tissues and can be diag- sulfate). Gardner7 and Stewart et al. 1° noted that these nosed if there is found to be more dermatan than lesions contain dense, fibrous connective tissues and heparan in tissues; while in Hurler’s syndrome,heparan large amounts of acid mucopolysaccharides. These ar- is more abundant. Other diagnostic characteristics in- eas of destruction also tend to worsen with age. The clude the patient’s physical features; dysostosis; gingival tissues are hyperplastic, hypertrophic, and dermatan or heparan in urine; enzyme studies show- enlarged, while the tongue is thickened and ing iduronate sulfatase deficiency in serum, white blood macroglossic2,2, 6, 7,10 The goal wouldbe to extract any cells, or cultured fibroblasts.1~ 2 cystically involved teeth, restore any carious teeth, and Hunter6 reported what have become the classical maintain oral health. Antibiotics should be given as a features of the syndrome bearing his name. The many prophylatic measure due to the heart conditions asso- primary systemic manifestations of Hunter’s syndrome ciated with Hunter’s syndrome. include macrocephaly, with the skull thickened and The temporomandibularjoint often shows a flatten- deformed, and the cranial base and orbital roofs be- ing of the articular surface, while the condyle maybe come thick and dense with the sagittal and lamboidal flattened or reduced in size accompanied by a large sutures closing prematurely. Very prominent frontal coronoid7 process with hypomotility. bossing and temporal bulges, as well as changes in the The teeth are small and shortened. There is general- skull can be present. As the children grow, they exhibit ized wideinterdental spacing.R, 6, 7,10,17 Theteeth can be moderate to severe developmental delay with peg-shaped and conical and often hypoplastic. Ante- hyperkinesis along with rough and uncoordinated be- 7 rior open-bites have been noted due to the enlarged havior.L2, 6, 7, 14, is Gardnerreportedthat these children protruding tongues, y, 17 There is delayed root forma- show resistance to discipline and are stubborn and tion, and the molars are often further posterior with a fearless, and becomeso difficult to managethat they distoangular tipping. 7 The palate is highly arched in are generally institutionalized. Their ability to speak manypatients with prominent palatal rugae. There are and walk decreases with age. He also noted that they deep grooves in the midsagittal plane and the alveolar have progressive difficulty in eating solid food and ridges are flattened7 The gingival tissues are that weight loss is common. hyperplastic, hypertrophic, and enlarged, while the Hunter6 and Dorfman1 reported problems with ton- tongueis thickenedand macroglossic.1, 2, 6, 7,10 sils and adenoids leading to frequent and severe respi- Hunter’s syndrome is diagnosed by a presence of ratory infections. Morehead and Parsons16 have re- the classical features reported by Hunter,6 Gorlin,2 and ported tracheobronchomalacia/major airway collapse. Dorfman2Clinical examinations, skeletal surveys, urine Skeletal abnormalities include an enlarged chest with and serum iduronate sulfatase analysis, psychomotor flaring ribs and short stature. The abnormalextremities tests, and genetic evaluations all have been used in show broad, claw-like short fingers. These children confirming Hunter’s syndrome2,2, 4, s exhibit hepatosplenomegaly due to the accumulation Bone marrow transplant (BMT) has been consid- of dermatan and heparan, which also causes cardiac ered a possible mode of treatment in patients with valvular disease resulting in distortion of the heart mucopolysaccharidosisbecause this is a stem cell dis- valves and thickening of the coronary arteries. Hirsutism order. 19 Warkentin et al. 2° reported that a BMTcould is noted and usually increases after age 2.1-3, 6 serve as a permanentsource of normal cells capable of Secondary systemic manifestations include frequent producing the deficient enzyme. This would permit otitis media resulting in hearing insufficiencies and the affected cells to degrade accumulated glycosami- progressive deafness.1-3, 6 noglycans and prevent further deposition. In BMT,lethal doses of chemotherapyand total body Death usually occurs due to cardiac or 16respiratory arrest.l-3, 6, 14 Morehead and Parsons reported radiation are used to completely destroy all bone mar- tracheobronchomalaciato be a part of respiratory com- row elements -- both malignant and normal cell lines plications. Liu17 and Gardner7 have reported that the -- thereby eliminating the inborn error of metabolism. mandible of the Hunter’s syndromepatient is usually A healthy donor’s cells are used to repopulate the mar- short
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